Abstract
Gestational stress may have lasting deleterious effects on neuro-cognitive development of offspring. Progesterone (P), and its 5α-reduced metabolites, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP), maintain pregnancy, and can have effects on cognitive performance and/or neuronal integrity. However, whether some of the deleterious effects of gestational stress on cognitive and neural processes may be related to progestogen formation is not known. Pregnant rat dams were exposed to a regimen of variable stressors (including forced swim, restraint, fasting, social stress, and exposure to cold and light) on gestational days 17-21 or were minimally-handled controls. Male and female offspring were cross-fostered to non-manipulated dams and assessed for motor and cognitive performance between postnatal days 28 and 30. Although the motor behavior of gestationally-stressed offspring did not differ significantly from control, offspring, their cognitive performance in an object recognition task was poorer. Irrespective of sex, dendritic spine density was reduced in dorsal hippocampus of stress-exposed offspring compared to control offspring. Formation of DHP was reduced in medial prefrontal cortex (mPFC) and increased in hippocampus of stressed, compared to control, offspring. Notably, there were sex differences wherein estradiol in mPFC, as well as P and DHP in diencephalon, were increased with stress among females but decreased with stress among males. These data suggest that exposure to variable stress during gestation can perturb cognitive performance, concomitant with dendrite development in hippocampus, and Ps 5α-reduction in hippocampus and mPFC. Some sex differences in stress effects on progestogen formation may occur in diencephalon.
Keywords: diencephalon, dendrite development in hippocampus, medial prefrontal cortex, offspring, neuronal integrity, cognitive performance, Gestational stress, progesterone, pregnancy, prenatal stress, open field, object recognition, dihydroprogesterone, Allopregnanolone
Current Topics in Medicinal Chemistry
Title: Gestational Exposure to Variable Stressors Produces Decrements in Cognitive and Neural Development of Juvenile Male and Female Rats
Volume: 11 Issue: 13
Author(s): Cheryl A. Frye and Jason J. Paris
Affiliation:
Keywords: diencephalon, dendrite development in hippocampus, medial prefrontal cortex, offspring, neuronal integrity, cognitive performance, Gestational stress, progesterone, pregnancy, prenatal stress, open field, object recognition, dihydroprogesterone, Allopregnanolone
Abstract: Gestational stress may have lasting deleterious effects on neuro-cognitive development of offspring. Progesterone (P), and its 5α-reduced metabolites, dihydroprogesterone (DHP) and 5α-pregnan-3α-ol-20-one (3α,5α-THP), maintain pregnancy, and can have effects on cognitive performance and/or neuronal integrity. However, whether some of the deleterious effects of gestational stress on cognitive and neural processes may be related to progestogen formation is not known. Pregnant rat dams were exposed to a regimen of variable stressors (including forced swim, restraint, fasting, social stress, and exposure to cold and light) on gestational days 17-21 or were minimally-handled controls. Male and female offspring were cross-fostered to non-manipulated dams and assessed for motor and cognitive performance between postnatal days 28 and 30. Although the motor behavior of gestationally-stressed offspring did not differ significantly from control, offspring, their cognitive performance in an object recognition task was poorer. Irrespective of sex, dendritic spine density was reduced in dorsal hippocampus of stress-exposed offspring compared to control offspring. Formation of DHP was reduced in medial prefrontal cortex (mPFC) and increased in hippocampus of stressed, compared to control, offspring. Notably, there were sex differences wherein estradiol in mPFC, as well as P and DHP in diencephalon, were increased with stress among females but decreased with stress among males. These data suggest that exposure to variable stress during gestation can perturb cognitive performance, concomitant with dendrite development in hippocampus, and Ps 5α-reduction in hippocampus and mPFC. Some sex differences in stress effects on progestogen formation may occur in diencephalon.
Export Options
About this article
Cite this article as:
A. Frye Cheryl and J. Paris Jason, Gestational Exposure to Variable Stressors Produces Decrements in Cognitive and Neural Development of Juvenile Male and Female Rats, Current Topics in Medicinal Chemistry 2011; 11 (13) . https://dx.doi.org/10.2174/156802611796117649
DOI https://dx.doi.org/10.2174/156802611796117649 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Endocannabinoid System in Neurological Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Blood-Brain Barrier Alterations in MDX Mouse, An Animal Model of the Duchenne Muscular Dystrophy
Current Neurovascular Research Update to Medicinal Chemistry of Nicotinamide in the Treatment of Ischemia and Reperfusion
Medicinal Chemistry Reviews - Online (Discontinued) Combined Treatment Fkt-Botulinum Toxin Type A (Btx-A) in Patients with Strumpell-Lorrain Disease
Current Pharmaceutical Design Chemokines and Chemokine Receptors: Potential Therapeutic Targets in Multiple Sclerosis
Current Drug Targets - Inflammation & Allergy Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management
Current Vascular Pharmacology From the Oxygen to the Organ Protection: Erythropoietin as Protagonist in Internal Medicine
Cardiovascular & Hematological Agents in Medicinal Chemistry EDITORIAL: Novel Signaling Pathway Based Therapeutics in Cancer and Other Diseases
Current Signal Transduction Therapy Combination Therapy for Multi-Target Manipulation of Secondary Brain Injury Mechanisms
Current Neuropharmacology Neuropsychiatric Disturbances in Alzheimer’s Disease: What Have We Learned from Neuropathological Studies?
Current Alzheimer Research Treating Asthma as a Neuroelectrical Disorder
Inflammation & Allergy - Drug Targets (Discontinued) A Comprehensive Review on Hydrogels
Current Drug Delivery Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis
Current Neuropharmacology Apoptosis Induction by Erucylphosphohomocholine via the 18 kDa Mitochondrial Translocator Protein: Implications for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Targeting Oxidative Stress Component in the Therapeutics of Epilepsy
Current Topics in Medicinal Chemistry Estrogen and Cytokines Production - The Possible Cause of Gender Differences in Neurological Diseases
Current Pharmaceutical Design Von Willebrand Factor and Thrombosis: Risk Factor, Actor and Pharmacological Target
Current Vascular Pharmacology The Pathogenesis of Neurotrauma Indicates Targets for Neuroprotective Therapies
Current Neuropharmacology Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews Exosomes and the Emerging Field of Exosome-Based Gene Therapy
Current Gene Therapy